ES2965746T3 - Procesos para producir brivaracetam - Google Patents
Procesos para producir brivaracetam Download PDFInfo
- Publication number
- ES2965746T3 ES2965746T3 ES16800643T ES16800643T ES2965746T3 ES 2965746 T3 ES2965746 T3 ES 2965746T3 ES 16800643 T ES16800643 T ES 16800643T ES 16800643 T ES16800643 T ES 16800643T ES 2965746 T3 ES2965746 T3 ES 2965746T3
- Authority
- ES
- Spain
- Prior art keywords
- compound
- formula
- alkyl
- xii
- brivaracetam
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- MSYKRHVOOPPJKU-BDAKNGLRSA-N brivaracetam Chemical compound CCC[C@H]1CN([C@@H](CC)C(N)=O)C(=O)C1 MSYKRHVOOPPJKU-BDAKNGLRSA-N 0.000 title claims abstract description 83
- 229960002161 brivaracetam Drugs 0.000 title claims abstract description 66
- 238000000034 method Methods 0.000 title claims description 49
- 150000001875 compounds Chemical class 0.000 claims description 177
- 238000006243 chemical reaction Methods 0.000 claims description 62
- 239000002904 solvent Substances 0.000 claims description 52
- 238000002360 preparation method Methods 0.000 claims description 49
- 229920006395 saturated elastomer Chemical group 0.000 claims description 21
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 16
- -1 alkyl (S)-2-aminobutanoate Chemical compound 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 11
- 229910052740 iodine Inorganic materials 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 238000007142 ring opening reaction Methods 0.000 claims description 6
- HNNJFUDLLWOVKZ-VKHMYHEASA-N (2s)-2-aminobutanamide Chemical compound CC[C@H](N)C(N)=O HNNJFUDLLWOVKZ-VKHMYHEASA-N 0.000 claims description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims description 4
- 238000006114 decarboxylation reaction Methods 0.000 claims description 4
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 2
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 3
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims 2
- 125000003860 C1-C20 alkoxy group Chemical group 0.000 claims 1
- 230000032050 esterification Effects 0.000 claims 1
- 238000005886 esterification reaction Methods 0.000 claims 1
- 239000011968 lewis acid catalyst Substances 0.000 claims 1
- 238000007363 ring formation reaction Methods 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 14
- 230000015572 biosynthetic process Effects 0.000 abstract description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
- 239000000243 solution Substances 0.000 description 52
- 238000005160 1H NMR spectroscopy Methods 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 41
- 239000012044 organic layer Substances 0.000 description 35
- 239000000203 mixture Substances 0.000 description 34
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 239000007832 Na2SO4 Substances 0.000 description 29
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 29
- 229910052938 sodium sulfate Inorganic materials 0.000 description 29
- 235000011152 sodium sulphate Nutrition 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 239000012043 crude product Substances 0.000 description 25
- 238000001704 evaporation Methods 0.000 description 25
- 230000008020 evaporation Effects 0.000 description 25
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
- 239000012267 brine Substances 0.000 description 24
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
- 238000001914 filtration Methods 0.000 description 23
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- BDMZQMSLGVUERW-IENPIDJESA-N ethyl (4r)-4-(2-methylpropyl)-2-oxooxolane-3-carboxylate Chemical compound CCOC(=O)C1[C@@H](CC(C)C)COC1=O BDMZQMSLGVUERW-IENPIDJESA-N 0.000 description 14
- 238000010898 silica gel chromatography Methods 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 229910052751 metal Inorganic materials 0.000 description 12
- 239000002184 metal Substances 0.000 description 12
- 238000005292 vacuum distillation Methods 0.000 description 12
- GSKKODFCGSQPLP-BDAKNGLRSA-N (3R)-N-[(2S)-1-amino-1-oxobutan-2-yl]-3-(chloromethyl)hexanamide Chemical compound NC([C@H](CC)NC(C[C@@H](CCC)CCl)=O)=O GSKKODFCGSQPLP-BDAKNGLRSA-N 0.000 description 10
- NVTUTJMZAZZKAZ-ZCFIWIBFSA-N (4r)-4-propyloxolan-2-one Chemical compound CCC[C@H]1COC(=O)C1 NVTUTJMZAZZKAZ-ZCFIWIBFSA-N 0.000 description 10
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical group [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 10
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical group [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 238000004296 chiral HPLC Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical group [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- FZNZMKYHAARKOO-XNCJUZBTSA-N ethyl (1s,5r)-2-oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylate Chemical compound C1OC(=O)[C@]2(C(=O)OCC)[C@H]1C2 FZNZMKYHAARKOO-XNCJUZBTSA-N 0.000 description 8
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- HPHUVLMMVZITSG-ZCFIWIBFSA-N levetiracetam Chemical compound CC[C@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-ZCFIWIBFSA-N 0.000 description 8
- 235000011118 potassium hydroxide Nutrition 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 229960004002 levetiracetam Drugs 0.000 description 7
- 235000011121 sodium hydroxide Nutrition 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- HYWPILIRWIBGKA-MRVPVSSYSA-N CCC[C@@H](CBr)CC(=O)OCC Chemical compound CCC[C@@H](CBr)CC(=O)OCC HYWPILIRWIBGKA-MRVPVSSYSA-N 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical group CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- HDBMIDJFXOYCGK-DFWYDOINSA-N (2s)-2-aminobutanamide;hydrochloride Chemical compound Cl.CC[C@H](N)C(N)=O HDBMIDJFXOYCGK-DFWYDOINSA-N 0.000 description 4
- VOMAAWRLZIQVIT-ZBHICJROSA-N (4R)-2-oxo-4-propyloxolane-3-carboxylic acid Chemical compound O=C1OC[C@@H](C1C(=O)O)CCC VOMAAWRLZIQVIT-ZBHICJROSA-N 0.000 description 4
- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000001961 anticonvulsive agent Substances 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- JCRGMKPHACPAII-ZJUUUORDSA-N methyl (2S)-2-[[(3R)-3-(chloromethyl)hexanoyl]amino]butanoate Chemical compound ClC[C@@H](CC(=O)N[C@H](C(=O)OC)CC)CCC JCRGMKPHACPAII-ZJUUUORDSA-N 0.000 description 4
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 4
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000012047 saturated solution Substances 0.000 description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 4
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 4
- BRLQWZUYTZBJKN-VKHMYHEASA-N (-)-Epichlorohydrin Chemical compound ClC[C@H]1CO1 BRLQWZUYTZBJKN-VKHMYHEASA-N 0.000 description 3
- NYIXDCWAFHWQTI-ZCFIWIBFSA-N (3R)-3-(chloromethyl)hexanoyl chloride Chemical compound ClC[C@@H](CC(=O)Cl)CCC NYIXDCWAFHWQTI-ZCFIWIBFSA-N 0.000 description 3
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 3
- 101000632319 Homo sapiens Septin-7 Proteins 0.000 description 3
- 102100027981 Septin-7 Human genes 0.000 description 3
- 239000000010 aprotic solvent Substances 0.000 description 3
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 3
- 206010015037 epilepsy Diseases 0.000 description 3
- QBZXOWQOWPHHRA-UHFFFAOYSA-N lithium;ethane Chemical compound [Li+].[CH2-]C QBZXOWQOWPHHRA-UHFFFAOYSA-N 0.000 description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000001103 potassium chloride Substances 0.000 description 3
- 235000011164 potassium chloride Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 2
- WVYWICLMDOOCFB-UHFFFAOYSA-N 4-methyl-2-pentanol Chemical compound CC(C)CC(C)O WVYWICLMDOOCFB-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010022998 Irritability Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 2
- 229910001623 magnesium bromide Inorganic materials 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 1
- XUBVYXDJGCTGTL-ZCFIWIBFSA-N (3R)-3-(bromomethyl)hexanoic acid Chemical compound BrC[C@@H](CC(=O)O)CCC XUBVYXDJGCTGTL-ZCFIWIBFSA-N 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 150000003869 acetamides Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000010568 chiral column chromatography Methods 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- HZVJPBPAJMKQEC-JAMMHHFISA-N ethyl (4R)-2-oxo-4-propyloxolane-3-carboxylate Chemical compound C(CC)[C@@H]1C(C(OC1)=O)C(=O)OCC HZVJPBPAJMKQEC-JAMMHHFISA-N 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropyl acetate Chemical compound CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- LOPBUDFWZJEGTJ-ZJUUUORDSA-N methyl (2s)-2-[(4r)-2-oxo-4-propylpyrrolidin-1-yl]butanoate Chemical compound CCC[C@H]1CN([C@@H](CC)C(=O)OC)C(=O)C1 LOPBUDFWZJEGTJ-ZJUUUORDSA-N 0.000 description 1
- AHAQQEGUPULIOZ-WCCKRBBISA-N methyl (2s)-2-aminobutanoate;hydrochloride Chemical compound Cl.CC[C@H](N)C(=O)OC AHAQQEGUPULIOZ-WCCKRBBISA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 208000005809 status epilepticus Diseases 0.000 description 1
- 210000002504 synaptic vesicle Anatomy 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/04—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups
- C07C209/06—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms
- C07C209/08—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms with formation of amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/14—Preparation of carboxylic acid amides by formation of carboxamide groups together with reactions not involving the carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C233/04—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C233/05—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
- C07C237/06—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
- C07C53/15—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen containing halogen
- C07C53/19—Acids containing three or more carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
- C07C53/38—Acyl halides
- C07C53/46—Acyl halides containing halogen outside the carbonyl halide group
- C07C53/50—Acyl halides containing halogen outside the carbonyl halide group of acids containing three or more carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/307—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/62—Halogen-containing esters
- C07C69/63—Halogen-containing esters of saturated acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C71/00—Esters of oxyacids of halogens
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510271449.6A CN106279074B (zh) | 2015-05-25 | 2015-05-25 | 一种化合物及其制备方法和在合成布瓦西坦中的用途 |
| CN201510430387.9A CN106365986B (zh) | 2015-07-21 | 2015-07-21 | 化合物及其制备方法和在合成布瓦西坦中的用途 |
| CN201510648574.4A CN106432030B (zh) | 2015-10-10 | 2015-10-10 | 布瓦西坦的一种制备方法 |
| CN201610099672 | 2016-02-24 | ||
| PCT/US2016/033965 WO2016191435A1 (en) | 2015-05-25 | 2016-05-24 | Processes to produce brivaracetam |
Publications (1)
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| ES2965746T3 true ES2965746T3 (es) | 2024-04-16 |
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| ES16800643T Active ES2965746T3 (es) | 2015-05-25 | 2016-05-24 | Procesos para producir brivaracetam |
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| Country | Link |
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| US (3) | US10221134B2 (enExample) |
| EP (1) | EP3302441B1 (enExample) |
| JP (1) | JP6872500B2 (enExample) |
| KR (1) | KR102630456B1 (enExample) |
| BR (1) | BR112017025266A2 (enExample) |
| CA (1) | CA2984832A1 (enExample) |
| ES (1) | ES2965746T3 (enExample) |
| HR (1) | HRP20240027T1 (enExample) |
| HU (1) | HUE064612T2 (enExample) |
| IL (1) | IL255880B (enExample) |
| MX (1) | MX380263B (enExample) |
| PL (1) | PL3302441T3 (enExample) |
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| CA2984832A1 (en) | 2015-05-25 | 2016-12-01 | Esteve Quimica S.A. | Processes to produce brivaracetam |
| CN107056643A (zh) * | 2017-03-01 | 2017-08-18 | 苏州鹏旭医药科技有限公司 | 一种化合物的晶型a及其制备纯化方法 |
| WO2018141276A1 (zh) * | 2017-02-05 | 2018-08-09 | 苏州鹏旭医药科技有限公司 | 布瓦西坦中间体的晶型a及其制备方法和布瓦西坦的晶型c及其制备方法 |
| CN108503573B (zh) * | 2017-02-24 | 2019-11-22 | 北京艾百诺医药股份有限公司 | 一种布瓦西坦的新的制备方法 |
| CN108503609B (zh) * | 2017-02-24 | 2019-12-24 | 北京艾百诺医药股份有限公司 | 一种制备光学纯的(r)-4-正丙基-二氢呋喃-2(3h)-酮的方法 |
| CN108689903B (zh) * | 2017-04-06 | 2019-12-24 | 北京艾百诺医药股份有限公司 | 一种布瓦西坦的新的制备方法 |
| WO2018220646A1 (en) * | 2017-05-29 | 2018-12-06 | Msn Laboratories Private Limited, R&D Center | An improved process for the preparation of (2s)-2-[(4r)-2-oxo-4-propyltetrahydro-1h-pyrrol-1-yl] butanamide and its intermediates thereof |
| WO2019087172A1 (en) * | 2017-12-19 | 2019-05-09 | Glenmark Pharmaceuticals Limited | Process for preparation of brivaracetam |
| CN108409557A (zh) * | 2018-05-17 | 2018-08-17 | 丽珠集团新北江制药股份有限公司 | 布瓦西坦新中间体及其合成方法和应用 |
| IT201800006320A1 (it) * | 2018-06-14 | 2019-12-14 | Processo per la sintesi asimmetrica di (r)-4-propildiidrofuran-2(3h)-one | |
| CN110615744B (zh) * | 2018-06-20 | 2023-01-06 | 上海朴颐化学科技有限公司 | 一种布瓦西坦中间体及其制备方法 |
| JP7117796B2 (ja) * | 2018-06-22 | 2022-08-15 | 福建▲海▼西新▲薬▼▲創▼制有限公司 | 化合物並びにブリバラセタム（Ｂｒｉｖａｒａｃｅｔａｍ）の中間体及び原薬の合成におけるその用途 |
| WO2020148787A1 (en) * | 2019-01-17 | 2020-07-23 | Clininvent Research Pvt. Ltd. | Enantioselective synthesis of brivaracetam and intermediates thereof |
| CN112110843A (zh) * | 2019-06-20 | 2020-12-22 | 北京万全德众医药生物技术有限公司 | 一种布瓦西坦的新制备方法 |
| WO2021260721A1 (en) * | 2020-06-23 | 2021-12-30 | Clininvent Research Pvt. Ltd. | A new cost effective and scalable process for synthesizing pure brivaracetam |
| ES3032398T3 (en) | 2020-12-14 | 2025-07-18 | Alivus Life Sciences Ltd | Process for the preparation of brivaracetam |
| US11400074B1 (en) * | 2021-02-01 | 2022-08-02 | Divi's Laboratories Ltd. | Enzymatic process for the preparation of (2S)-2-[(4R)-2-oxo-4-propyl-pyrrolidin-1-yl]butyric acid and its conversion into brivaracetam |
| US20240343689A1 (en) * | 2021-08-16 | 2024-10-17 | Optimus Drugs Private Limited | Synthesis of brivaracetam |
| CN114634437B (zh) * | 2022-03-29 | 2023-05-30 | 武汉氟本氘合新材料科技有限公司 | 一种布瓦西坦的简易制备方法 |
| CN114989061A (zh) * | 2022-08-03 | 2022-09-02 | 江苏同禾药业有限公司 | 一种布瓦西坦的制备方法 |
| CN115466233B (zh) * | 2022-09-28 | 2024-08-23 | 合肥立方制药股份有限公司 | 一种布瓦西坦中间体（r）-4-丙基-二氢呋喃-2-酮的合成方法 |
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| AU2002329233B2 (en) * | 2001-08-10 | 2007-08-16 | Ucb Pharma | Oxopyrrolidine compounds, preparation of said compounds and their use in the manufacturing of levetiracetam and analogues |
| JP4658937B2 (ja) | 2003-09-24 | 2011-03-23 | ユセベ ファルマ ソシエテ アノニム | ２−オキソ−１−ピロリジン誘導体の製造方法 |
| TW200724139A (en) * | 2005-05-05 | 2007-07-01 | Warner Lambert Co | Androgen modulators |
| CA2620243C (en) | 2005-09-15 | 2015-01-20 | Ucb Pharma, S.A. | 4-substituted pyrrolidin-2-ones and their use |
| AU2006322297A1 (en) | 2005-12-07 | 2007-06-14 | Ucb Pharma, S.A. | 3-carboxy- 2-oxo-1 -pyrrolidine derivatives and their uses |
| US8338621B2 (en) | 2005-12-21 | 2012-12-25 | Ucb S.A. | Process for the preparation of 2-oxo-1-pyrrolidine derivatives |
| KR20070081959A (ko) | 2006-02-14 | 2007-08-20 | (주)지앤테크 | 은이 포함된 정수기용 필터 |
| KR100846419B1 (ko) | 2007-08-10 | 2008-07-15 | 한국과학기술원 | 프레가발린의 신규한 제조 방법 |
| KR100915671B1 (ko) * | 2007-08-14 | 2009-09-04 | 한국과학기술원 | 치환된 γ-부티로락톤의 광학선택적 제조방법 |
| WO2010111622A2 (en) * | 2009-03-27 | 2010-09-30 | Codexis, Inc. | Amidases and methods of their use |
| EP2571352A4 (en) | 2010-05-21 | 2014-09-17 | Sloan Kettering Inst Cancer | SELECTIVE HDAC HEMMER |
| WO2012140504A1 (en) | 2011-04-11 | 2012-10-18 | Rubhana Raqib | Therapeutic compounds |
| US20140228579A1 (en) | 2013-02-14 | 2014-08-14 | Brock Unviersity | Method for the catalytic reduction of acid chlorides and imidoyl chlorides |
| CN103819389A (zh) * | 2014-02-17 | 2014-05-28 | 北京博泽德润医药科技开发有限公司 | 一种左乙拉西坦制备方法 |
| CA2984832A1 (en) | 2015-05-25 | 2016-12-01 | Esteve Quimica S.A. | Processes to produce brivaracetam |
| RS62472B1 (sr) | 2015-11-03 | 2021-11-30 | UCB Biopharma SRL | Postupak pripreme brivaracetama |
| WO2018220646A1 (en) | 2017-05-29 | 2018-12-06 | Msn Laboratories Private Limited, R&D Center | An improved process for the preparation of (2s)-2-[(4r)-2-oxo-4-propyltetrahydro-1h-pyrrol-1-yl] butanamide and its intermediates thereof |
| WO2019087172A1 (en) | 2017-12-19 | 2019-05-09 | Glenmark Pharmaceuticals Limited | Process for preparation of brivaracetam |
| WO2020148731A1 (en) | 2019-01-19 | 2020-07-23 | Stereokem Pvt. Ltd. | Process for preparation of brivaracetam intermediates and use thereof |
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2019
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| EP3302441A1 (en) | 2018-04-11 |
| US11673862B2 (en) | 2023-06-13 |
| JP2018523633A (ja) | 2018-08-23 |
| MX380263B (es) | 2025-03-12 |
| US10221134B2 (en) | 2019-03-05 |
| US20190152909A1 (en) | 2019-05-23 |
| US20240199541A9 (en) | 2024-06-20 |
| EP3302441A4 (en) | 2019-01-09 |
| EP3302441B1 (en) | 2023-12-13 |
| HRP20240027T1 (hr) | 2024-04-26 |
| BR112017025266A2 (pt) | 2018-08-07 |
| US20190152908A1 (en) | 2019-05-23 |
| IL255880A (en) | 2018-01-31 |
| US20180155284A1 (en) | 2018-06-07 |
| EP3302441C0 (en) | 2023-12-13 |
| CA2984832A1 (en) | 2016-12-01 |
| JP6872500B2 (ja) | 2021-05-19 |
| KR102630456B1 (ko) | 2024-01-29 |
| WO2016191435A1 (en) | 2016-12-01 |
| US12221413B2 (en) | 2025-02-11 |
| HUE064612T2 (hu) | 2024-04-28 |
| KR20180012788A (ko) | 2018-02-06 |
| PL3302441T3 (pl) | 2024-05-20 |
| IL255880B (en) | 2021-02-28 |
| MX2017015133A (es) | 2018-08-01 |
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